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The prognosis of primary CNS lymphoma (PCNSL) is poor. The trend has been to treat without the use of whole brain radiation, as results with chemotherapy are better, and adding radiation to chemotherapy is thought to add toxicity. This study attempted to investigate the use of chemotherapy vs. chemotherapy plus radiation therapy in a randomized setting.

Evaluation of response was done after the treatment with this primary chemotherapy. If no CR was obtained, treatment with further chemotherapy (ifosfamide 3mg/m2 and idarubicin 12 mg/m2 or high dose araC) was done.

If CR was obtained, patients were randomized to receive radiation therapy to 45 Gy vs. one additional chemotherapy course.

Results

30/56 patients obtained CR after methotrexate based chemotherapy regimen. An additional 4 patients obtained CR after salvage chemotherapy with idarubicin and ifosfamide. Therefore, 34 patients were available for randomization.

Because of toxicity, death, refusal, etc., only 23 patients were actually randomized (12 to further chemotherapy, 11 to radiation therapy)

4 patients randomized to radiation therapy refused treatment

OS was 20.8 months

OS in radiation group was 27.8 months vs. 21.2 months in the chemotherapy arm (p=NS)

Median time to progression was 9.4 months

Late neurotoxicity was seen in 8/56 patients (14%). All neurotoxicity was noted after 1 year of treatment

Incidence of late neurotoxicity was 27% in those not irradiatied vs. 7% in those irradiated

Author's Conclusions

Few patients will accept combined chemoradiation for treatment of PCNSL due to toxicity, declining status, or death

The number of patients receiving radiation was small, but there was no increased incidence of neurotoxicity in these patients

Clinical/Scientific Implications

The treatment of primary CNS lymphoma has changed over the past several years. It has classically been treated with radiation alone, though encouraging results with the use of methotrexate based chemotherapy has led to the standard of care shifting toward using chemotherapy. Radiation has not been used in these patients routinely because of the possible risk of neurotoxicity. Although, because of small numbers, definitive conclusions cannot be made regarding this issue based on this study, there are other observations that should be noted. First, it points to how poorly these patients do, with a significant proportion dying or experiencing a decline in function before randomization could even occur. There is also a significant mortality within 1 year. With all neurotoxicity seen in these patients occurring after 1 year, this will likely never be a factor in many of these patients. Time to progression is also short (9.4 months). Therefore, it will be very difficult to assign a decline in neurologic function to radiation vs. progression of lymphomatous disease.